Enhanced polyadenosine diphosphate‐ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma

Shiobara, Masayuki; Miyazaki, Masaru; Ito, Hiroshi; Togawa, Akira; Nakajima, Nobuyuki; Nomura, Fumio; Morinaga, Naoko; Noda, Masatoshi

doi:10.1046/j.1440-1746.2001.02378.x

Cited by 70 publications

(47 citation statements)

References 29 publications

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“…Consistent with these findings are the data from a number of PARP inhibitors based on nicotinamide analogues, ranging from those with low micromolar activity, such as 3-aminobenzamide (Durkacz et al, 1980) to the more potent and specific PARP inhibitors that have been generated more recently (Southan and Szabo, 2003;Curtin, 2005;Farmer et al, 2005;Ratnam and Low, 2007). Enhanced PARP-1 expression or activity has been observed in a number of different tumour cell lines (Tomoda et al, 1991;Shiobara et al, 2001) and could provide a greater level of resistance to both endogenous genotoxic stress, as well as to DNA damage-inducing therapeutic agents. Evidence that PARP inhibitors can sensitize tumour cells to cytotoxic therapies such as temozolomide, topoisomerase I inhibitors, platinums and radiation (for example Calabrese et al, 2004;Miknyoczki et al, 2003;Chalmers et al, 2004) has consequently provided sufficient interest for a number of these compounds to be developed as clinical candidates (see Table 2 and Plummer, 2005;Fong et al, 2006).…”

Section: Inhibitors Of Parpmentioning

confidence: 55%

Targeted cancer therapies based on the inhibition of DNA strand break repair

2007

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Both DNA double-and single-strand break repair are highly coordinated processes utilizing signal transduction cascades and post-translational modifications such as phosphorylation, acetylation and ADP ribosylation. 'Drugable' targets within these networks have been identified that could potentially lead to novel therapeutic approaches within the oncology arena. Key regulators within these signalling cascades, such as DNA-dependent protein kinase, ataxia-telangiectasia mutated, checkpoint kinase 1 (CHK1), checkpoint kinase 2 (CHK2) and poly(ADPribose) polymerase, use either ATP or nicotinamide adenine dinucleotide for their enzymatic functions and are therefore readily accessible to small molecule inhibition at their catalytic sites. A range of highly potent and selective inhibitors of these DNA damage response pathways has now been identified through drug discovery efforts, with candidate molecules either approaching or already in clinical trials. This review will describe the small molecule inhibitors and drug discovery activities that focus on DNA break repair, along with the therapeutic rationale behind chemosensitization and the concept of synthetic lethality. We will also describe the emerging clinical data coming from this exciting new approach to targeted cancer therapy.

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Section: Inhibitors Of Parpmentioning

confidence: 55%

Targeted cancer therapies based on the inhibition of DNA strand break repair

2007

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“…pArp-1 is involved in DnA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death as well as a master component of a number of transcription factors involved in tumor development and inflammation (8). overexpression of pArp-1 has been reported in various human malignancies, such as malignant lymphoma (9), breast carcinoma (10), ewing's sarcoma (11), Hcc (12) and in the U2os human osteosarcoma cell line (13). As pArp-1 actively participates in DnA repair, pArp-1 inhibitors have been applied in cancer treatment either alone or in combination with DnA-damaging agents (14).…”

Section: Introductionmentioning

confidence: 99%

The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells

Zheng

Xu²,

Peng³

et al. 2011

Oncol Rep

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Abstract. pharmacological inhibition of DnA repair pathways has been emerging as an effective tool for cancer treatment. poly(ADp-ribose) polymerase (pArp) is involved in DnA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death. In vitro and in vivo data suggest that pArp inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancer cells in certain types of tumors. In the present study, we investigate the effects of 3-aminobenzamide (3-AB), a potent inhibitor of pArp, on human osteosarcoma cells and whether or not it can sensitize the tumor cells to chemotherapeutic agents. the results indicated that 3-AB suppressed U2os cell growth in a time-and dose-dependent manner, and the suppressive effects of 3-AB were associated with increased cell apoptosis. In addition, 3-AB suppressed cell invasion in vitro and enhanced the suppressive effects of cisplatin in U2os cells. our work suggests that this pArp-1 inhibitor may be developed into an effective agent for the treatment of human osteosarcoma.

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“…For example, PARP mRNA levels were found to be enhanced in malignant lymphomas but not in normal lymph nodes or reactive proliferative lymph nodes (17). Elevated PARP activity was identified in peripheral lymphocytes from patients with low-grade malignant non -Hodgkin's lymphoma (18), hepatocellular carcinomas (19,20), small-cell lung cancer lines (21), cervical cancer cells from patients (22), and the prostate cancer cell line LnCaP (23). Elevated PARP expression has also been shown to be associated with chemoresistance (21).…”

Section: Introductionmentioning

confidence: 99%

Potentiation of Temozolomide Cytotoxicity by Poly(ADP)Ribose Polymerase Inhibitor ABT-888 Requires a Conversion of Single-Stranded DNA Damages to Double-Stranded DNA Breaks

Liu¹,

Shi²,

Guan³

et al. 2008

Molecular Cancer Research

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Poly(ADP-ribose) polymerase (PARP) senses DNA breaks and facilitates DNA repair via the polyADP-ribosylation of various DNA binding and repair proteins. We explored the mechanism of potentiation of temozolomide cytotoxicity by the PARP inhibitor ABT-888. We showed that cells treated with temozolomide need to be exposed to ABT-888 for at least 17 to 24 hours to achieve maximal cytotoxicity. The extent of cytotoxicity correlates with the level of double-stranded DNA breaks as indicated by ;H2AX levels. In synchronized cells, damaging DNA with temozolomide in the presence of ABT-888 during the S phase generated high levels of double-stranded breaks, presumably because the single-stranded DNA breaks resulting from the cleavage of the methylated nucleotides were converted into double-stranded breaks through DNA replication. As a result, treatment of temozolomide and ABT-888 during the S phase leads to higher levels of cytotoxicity. ABT-888 inhibits poly(ADP-ribose) formation in vivo and enhances tumor growth inhibition by temozolomide in multiple models. ABT-888 is well tolerated in animal models. ABT-888 is currently in clinical trials in combination with temozolomide. (Mol Cancer Res 2008;6(10):1621 -9)

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Enhanced polyadenosine diphosphate‐ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma

Cited by 70 publications

References 29 publications

Targeted cancer therapies based on the inhibition of DNA strand break repair

Targeted cancer therapies based on the inhibition of DNA strand break repair

The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells

Potentiation of Temozolomide Cytotoxicity by Poly(ADP)Ribose Polymerase Inhibitor ABT-888 Requires a Conversion of Single-Stranded DNA Damages to Double-Stranded DNA Breaks

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